α-allenic alcohol is a very important intermediate in organic syntheses, and is widely used in the syntheses of organic compounds such as 2, 5-dihydrofuran (R. Gelin, S. Gelin, M. Albrand, Bull. Soc. Chim. Fr. 1972, 1946; L.-I. Olsson, A. Claesson, Synthesis 1979, 743; S. S. Nikam, K.-H. Chu, K. K. Wang, J. Org. Chem. 1986, 51, 745; J. A. Mashall, X.-J. Wang, J. Org. Chem. 1990, 55, 2995; J. A. Mashall, X.-J. Wang, J. Org. Chem. 1991, 56, 4913; J. A. Mashall, K. G. Pinney, J. Org. Chem. 1993, 58, 7180; J. A. Mashall, R. H. Yu, J. F. Perkins, J. Org. Chem. 1995, 60, 5550; J. A. Mashall, C. A. Sehon, J. Org. Chem. 1995, 60, 5966), 2(5H)-furanone (E. Yoneda, T. Kaneko, S.-W. Zhang, K. Onitsuka, S. Takahashi, Org. Lett. 2000, 2, 441; X. Cheng, X. Jiang, Y. Yu, S. Ma, J. Org. Chem. 2008, 73, 8960), ethyl-oxacyclopropane (R. W. Friesen, M. Blouin, J. Org. Chem. 1993, 58, 1653; S.-K. Kang, T. Yamaguchi, S.-J. Pyun, Y.-T. Lee, T.-G. Bail, Tetrahedron Lett. 1998, 39, 2127; S. Ma, S. Zhao, J. Am. Chem. Soc. 1999, 121, 7943), β-halo-β,γ-olefine aldehydes or β-halo-β,γ-olefine ketones (J. Li, C. Fu, G. Chen, G. Chai, S. Ma, Adv. Synth. Catal. 2008, 350, 1376; C. Fu, J. Li, S. Ma, Chem. Commun. 2005, 4119; J.-Q. He, D. Shibata, C. Ohno, S. Okamoto, Tetrahedron Lett. 2008, 49, 6724), 1, 3-conjugated dienes (S. Ma, G. Wang, Tetrahedron Lett. 2002, 43, 5723; Y. Deng, X. Jin, S. Ma, J. Org. Chem. 2007, 72, 5901) and allyl alcohols (Z. Lu, S. Ma, Adv. Synth. Catal. 2007, 349, 1225). Also, α-allenic alcohol is an important precuror for synthesizing a series of functionalized allenic compounds such as allenic amines (C. Sahlberg, S. B. Ross, I. Fagervall, A.-L. Ask, A. Claesson, J. Med. Chem. 1983, 26, 103; Y. Imada, M. Nishida, K. Kutsuwa, S.-I. Murahashi, T. Naota, Org. Lett. 2005, 7, 5837; B. M. Trost, D. R. Fandrick, D. C. Dinh, J. Am. Chem. Soc. 2005, 127, 14186), allenic malonate (M. Ogasawara, H. Ikeda, T. Nagano, T. Hayashi, J. Am. Chem. Soc. 2001, 123, 2089; Y. Imada, K. Ueno, K. Kutsuwa, S.-I. Murahashi, Chem. Lett. 2002, 140; S. Ma, N. Jiao, S. Zhao, H. Hou, J. Org. Chem., 2002, 67, 2837) allenyl mercaptan (N. Morita, N. Krause, Angew. Chem., Int. Ed. 2006, 45, 1897) and allenyl aldehydes or ketones (S. Ma, S. Yu, S. Yin, J. Org. Chem. 2003, 68, 8996; b) S. Ma, J. Liu, S. Li, B. Chen, J. Cheng, J. Kuang, Y. Liu, B. Wan, Y. Wang, J. Ye, Q. Yu, W. Yuan, S. Yu, Adv. Synth. Catal. 2011, 353, 1005). Among a series of α-allenic alcohols, axially chiral α-allenic alcohols are particularly important, because the axial chirality can be converted to central chirality by the chirality transferring strategy, which provides an effective route for synthesizing optically active compounds. Therefore, it is very significant to develop a method for conveniently and effectively synthesizing highly optically active axially chiral α-allenic alcohols. It's been reported that the syntheses of axially chiral α-allenic alcohols usually required complicated multiple steps and strict reaction conditions, and the total yields were very low. Moreover, most of those methods use dangerous chemicals such as n-butyllithium (n-BuLi), or ethylmagnesium bromide (EtMgBr) and lithium aluminum hydroxide (LiAlH4), which results in an inconvenient operation and is unsuitable for the syntheses in large scale (L.-I. Olsson, A. Claesson, Acta Chem. Scand. 1977, B31, 614; A. Claesson, L.-I. Olsson, J. Am. Chem. Soc. 1979, 101, 7302; R. A. Smith, R. L. White, A. Krantz, J. Med. Chem. 1988, 31, 1558; J. Stichler-Bonaparte, H. Kruth, R. Lunkwitz, C. Tschierske, Liebigs Ann. 1996, 1375).
The present invention overcomes the defects of the prior arts such as long synthetic route, low yield, the use of dangerous chemicals and inconvenient operations etc., and provides a method for conveniently and effectively preparing a highly optically active axially chiral α-allenic alcohol by using a propargyl alcohol protected by tert-butyldimethylsilyl group, an aldehyde and a chrial α, α-diphenylprolinol as reagents and by using zinc bromide as a mediator. As compared with the conventional methods, the present method has the advantages of short synthetic route, high yield, convenient operation, and good suitability for the synthesis in large scale.